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101.
The IL-21 receptor augments Th2 effector function and alternative macrophage activation 总被引:6,自引:0,他引:6
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Pesce J Kaviratne M Ramalingam TR Thompson RW Urban JF Cheever AW Young DA Collins M Grusby MJ Wynn TA 《The Journal of clinical investigation》2006,116(7):2044-2055
The IL-21 receptor (IL-21R) shows significant homology with the IL-4R, and CD4+ Th2 cells are an important source of IL-21. Here we examined whether the IL-21R regulates the development of Th2 responses in vivo. To do this, we infected IL-21R-/- mice with the Th2-inducing pathogens Schistosoma mansoni and Nippostrongylus brasiliensis and examined the influence of IL-21R deficiency on the development of Th2-dependent pathology. We showed that granulomatous inflammation and liver fibrosis were significantly reduced in S. mansoni-infected IL-21R-/- mice and in IL-21R+/+ mice treated with soluble IL-21R-Fc (sIL-21R-Fc). The impaired granulomatous response was also associated with a marked reduction in Th2 cytokine expression and function, as evidenced by the attenuated IL-4, IL-13, AMCase, Ym1, and FIZZ1 (also referred to as RELMalpha) responses in the tissues. A similarly impaired Th2 response was observed following N. brasiliensis infection. In vitro, IL-21 significantly augmented IL-4Ralpha and IL-13Ralpha1 expression in macrophages, resulting in increased FIZZ1 mRNA and arginase-1 activity following stimulation with IL-4 and IL-13. As such, these data identify the IL-21R as an important amplifier of alternative macrophage activation. Collectively, these results illustrate an essential function for the IL-21R in the development of pathogen-induced Th2 responses, which may have relevance in therapies for both inflammatory and chronic fibrotic diseases. 相似文献
102.
Jones OM Ramalingam T Merrie A Cunningham C George BD Mortensen NJ Lindsey I 《Diseases of the colon and rectum》2006,49(10):1574-1580
Purpose This study was designed to assess whether addition of glyceryl trinitrate to botulinum toxin improves the healing rate of
glyceryl trinitrate-resistant fissures over that achieved with botulinum toxin alone.
Methods Patients were randomized between botulinum toxin plus glyceryl trinitrate (Group A) and botulinum toxin plus placebo paste
(Group B). Patients were seen at baseline, four and eight weeks, and six months. The primary end point was fissure healing
at eight weeks. Secondary end points were symptomatic relief, need for surgery, side effects, and reduction in maximum resting
and squeeze pressures.
Results Thirty patients were randomized. Two-thirds of patients had maximum anal resting pressures below or within the normal range
at entry to the study. Healing rates in both treatment groups were disappointing. There was a nonsignificant trend to better
outcomes in Group A compared with Group B in terms of fissure healing (47 vs. 27 percent), symptomatic improvement (87 vs. 67 percent), and resort to surgery (27 vs. 47 percent).
Conclusions There is some evidence to suggest that combining glyceryl trinitrate with botulinum toxin is superior to the use of botulinum
toxin alone for glyceryl trinitrate-resistant anal fissure. The poor healing rate may reflect the fact that many of the patients
did not have significant anal spasm at trial entry.
Presented at the Tripartite Meeting in Dublin, Ireland, July 5 to 7 2005.
Supported by the Colorectal Research Fund, University of Oxford. Allergan supplied Botox™ for the study free of charge. They
did not contribute otherwise financially or intellectually to the study. 相似文献
103.
104.
Ramalingam Peraman Devanna Nayakanti Hari Hara Theja Dugga Sudhakara Kodikonda 《Scientia pharmaceutica》2013,81(4):1017-1028
A validated stability-indicating RP-HPLC method for etofenamate (ETF) was developed by separating its degradation products on a C18 (250 mm × 4.6 mm 5 μm) Qualisil BDS column using a phosphate buffer (pH-adjusted to 6.0 with orthophosphoric acid) and methanol in the ratio of 20:80 % v/v as the mobile phase at a flow rate of 1.0 mL/min. The column effluents were monitored by a photodiode array detector set at 286 nm. The method was validated in terms of specificity, linearity, accuracy, precision, detection limit, quantification limit, and robustness. Forced degradation of etofenamate was carried out under acidic, basic, thermal, photo, and peroxide conditions and the major degradation products of acidic and basic degradation were isolated and characterized by 1H-NMR, 13C-NMR, and mass spectral studies. The mass balance of the method varied between 92–99%. 相似文献
105.
Pelin Çıkla Esra Tatar İlkay Küçükgüzel Fikrettin Şahin Dilşad Yurdakul Amartya Basu Ramalingam Krishnan Daniel Brian Nichols Neerja Kaushik-Basu Ş. Güniz Küçükgüzel 《Medicinal chemistry research》2013,22(12):5685-5699
A novel series of new flurbiprofen hydrazide derivatives 2-(2-fluorobiphenyl-4-yl)-N′-[(substituted phenyl/5-nitro-2-furyl)methylene]propanehydrazide (3a–k), 2-(2-fluorobiphenyl-4-yl)-N-(2-substituted-4-oxo-1,3-thiazolidine-3-yl)propanamide (4a–b, 4d–k), 2-[2-(2-fluorobiphenyl-4-yl) propanoyl]-N-substituted hydrazinecarbothioamide (5a–h) and 2-(2-fluorobiphenyl-4-yl)-N′-[(3-methyl-4-oxo-1,3-thiazolidin-2-ylidene]propanehydrazide (6a–b, 6e and 6g) has been synthesized in this study. All synthesized compounds were screened for antimicrobial activity against various bacterial and fungal strains. Additionally, compounds were evaluated for the ability to inhibit Hepatitis C virus NS5B polymerase. The most active 4-thiazolidinone compound was 4k (SGK119) with 67.0 % and thiosemicarbazide compound was 5d (SGK123) with 69.50 % inhibition at 200 μM against hepatitis C virus NS5B RNA polymerase. Anticancer activity of the selected compounds (3i, 3j, 3h, 4d, 4i and 6b) was determined at a single dose towards the full panel of 60 human cancer cell lines by the National Cancer Institute (NCI). 2-(2-Fluoro-4-biphenylyl)-N-[2-[4-(trifluoromethyl)phenyl]-4-oxo-1,3-thiazolidine-3-yl]propanamide 4d, containing thiazolidinone ring, demonstrated the most marked effect with 20.80 % growth percent on leukaemia cancer cell line SR at 10?5 M. The results demonstrated that none of the compounds tested have anticandidal and antifungal activities, but two of them (4a and 4i) showed antibacterial inhibition against Micrococcus luteus, and Staphylococcus cohnii and Staphylococcus aureus, respectively. 相似文献
106.
107.
Senthilmurugan Ramalingam Lalji Gediya Andrew K. Kwegyir-Afful Vidya P. Ramamurthy Puranik Purushottamachar Hannah Mbatia Vincent C. O. Njar 《Oncotarget》2014,5(2):530-543
Some retinoic acid metabolism blocking agents (RAMBAs) are known to exhibit a wide range of anticancer activities by mechanisms that are still not completely resolved. This study investigated the anticancer efficacy and mechanism(s) of novel RAMBA retinamides (RRs) in triple negative and Her-2 overexpressing breast cancer cells. Specifically, we examined the possibility that RRs affect the translational machinery in these breast cancer (BC) cells. Recent findings suggest that overexpression of eukaryotic translation initiation factor 4E (eIF4E) in breast cancers critically augments CAP-dependent mRNA translation and synthesis of proteins involved in cell growth, cell proliferation, invasion and apoptosis evasion. The oncogenic potential of eIF4E is strictly dependent on serine209 phosphorylation by upstream MAPK-interacting kinases (Mnks). Targeting Mnk/eIF4E pathway for blocking Mnk function and eIF4E phosphorylation is therefore a novel approach for treating BCs, particularly for Her2-positive and triple negative breast cancers that have no indications for endocrine therapy or effective treatment regimes. We report for the first time that the degradation of Mnk1 by RRs in BC cells blocks eIF4E phosphorylation and subsequently inhibits cell growth, colonization, invasion, and migration and induce apoptosis. Most importantly, the anticancer efficacy of RRs was mediated via degrading Mnk rather than inhibiting its kinase activity like Mnk inhibitors (cercosporamide and ). Furthermore, RRs potencies on peIF4E down-regulation and growth inhibition were superior to those of two clinically relevant retinoids and the Mnk inhibitors. Together our findings provide the first preclinical proof-of-concept of novel Mnk degrading agents for Mnk/eIF4E based therapeutic treatment of breast cancers. CGP57380相似文献
108.
Ramalingam TR Pesce JT Sheikh F Cheever AW Mentink-Kane MM Wilson MS Stevens S Valenzuela DM Murphy AJ Yancopoulos GD Urban JF Donnelly RP Wynn TA 《Nature immunology》2008,9(1):25-33
The interleukin 4 receptor (IL-4R) is a central mediator of T helper type 2 (T(H)2)-mediated disease and associates with either the common gamma-chain to form the type I IL-4R or with the IL-13R alpha1 chain (IL-13Ralpha1) to form the type II IL-4R. Here we used Il13ra1-/- mice to characterize the distinct functions of type I and type II IL-4 receptors in vivo. In contrast to Il4ra-/- mice, which have weak T(H)2 responses, Il13ra1-/- mice had exacerbated T(H)2 responses. Il13ra1-/- mice showed much less mortality after infection with Schistosoma mansoni and much more susceptibility to Nippostrongylus brasiliensis. IL-13Ralpha1 was essential for allergen-induced airway hyperreactivity and mucus hypersecretion but not for fibroblast or alternative macrophage activation. Thus, type I and II IL-4 receptors exert distinct effects on immune responses. 相似文献
109.
Ramalingam P Adeagbo B Bollag R Lee J Reid-Nicholson M 《Diagnostic cytopathology》2008,36(10):742-748
CD138 is a monoclonal anti-syndecan-1 antibody that is often used to identify plasma cells in the bone marrow of patients with multiple myeloma (MM). Several carcinomas may also express CD138 including prostate, colon, renal cell, and hepatocellular carcinoma (HCC). We report a case of metastatic HCC that presented as a soft tissue mass on the back of a 67-year-old male. Based on the clinical and radiologic findings, MM was strongly suspected. In addition, fine-needle aspiration biopsy (FNAB) of the mass revealed neoplastic cells that were positive for CD138, both by immunohistochemistry (IHC) and flow cytometry. The cytomorphologic features however did not support a diagnosis of MM, but were consistent with metastatic HCC. Our case highlights the potential problems that may arise by over-reliance on IHC and flow cytometry. Careful morphologic assessment as well as clinical and radiologic correlation are very important when evaluating any CD138-positive neoplasm. This approach should improve diagnostic accuracy and reduce the risk of erroneous interpretation of aberrant IHC results. In addition, we examined the expression of CD138 in known cases of HCC. 相似文献
110.
S Sudharsanam S Swaminathan A Ramalingam G Thangavel R Annamalai R Steinberg K Balakrishnan P Srikanth 《African health sciences》2012,12(2):217-225